The importance of how a protein reconfigures its structure to achieve its function has long been appreciated; yet, the progress in our fundamental understanding of protein dynamics does not seem to be commensurate with the rapid advances in experimental techniques and ever increasing computational prowess. In this review, we attempt to look at this issue based on quantitative characterisations that go beyond simply determining the kinetics rates or only allowing qualitative statements about conformational states. We summarise the theoretical basis for determining from experimental data the kinetics and the structural elements of protein conformational dynamics. The two kinetics elements include the apparent potential of mean force and the intra-molecular diffusion coefficient along a coordinate defined by the pair of single-molecule Förster-type resonance energy transfer reporters that are chemically attached to the protein. We show that it is now possible to resolve the relative contributions of these two kinetics elements when discussing the physical origin of the protein’s conformation-reconfiguration rate changes due to mutation or interaction with chemical effectors or with other proteins. The structural element refers to the orthogonal conformational modes that give rise to the intrinsic conformational motions of the protein, and could allow a comparative study among proteins from different families. To achieve these, it is essential that experimental data be rigorously analysed and integrated with molecular simulations – which include molecular dynamics simulations, coarse-grained modelling, and enhanced sampling. In turn, the close interplay between computation and experiment through this new direction could accelerate the discovery of predictive models.

中文翻译：

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识别蛋白质大振幅构象运动中的结构和动力学元素

长期以来，人们一直认识到蛋白质如何重新配置​​其结构以实现其功能的重要性。然而，我们对蛋白质动力学的基本理解的进展似乎与实验技术的快速进步和不断提高的计算能力不相称。在这篇综述中，我们试图基于定量表征来研究这个问题，而不仅仅是简单地确定动力学速率或只允许关于构象状态的定性陈述。我们总结了从实验数据确定蛋白质构象动力学的动力学和结构要素的理论基础。这两个动力学元素包括平均力的表观电位和分子内扩散系数，沿着由化学连接到蛋白质的一对单分子 Förster 型共振能量转移报告基因定义的坐标。我们表明，在讨论由于突变或与化学效应物或其他蛋白质相互作用而导致的蛋白质构象重构率变化的物理起源时，现在可以解决这两个动力学元素的相对贡献。结构元素是指引起蛋白质固有构象运动的正交构象模式，可以对来自不同家族的蛋白质进行比较研究。为了实现这些，必须严格分析实验数据并将其与分子模拟相结合——包括分子动力学模拟、粗粒度建模和增强采样。反过来，通过这个新方向，计算和实验之间的密切相互作用可以加速预测模型的发现。